Dual receptor antagonistic antigen-binding proteins and uses thereof

Patent metadata

Field	Value
Publication number	US-2024327526-A1
Application number	US-202318381745-A
Country	US
Kind code	A1
Filing date	Oct 19, 2023
Priority date	Jun 11, 2012
Publication date	Oct 3, 2024
Grant date	—

Abstract

This disclosure related to antagonistic dual receptor antigen-binding proteins, e.g. antibodies and methods of using the dual receptor antibodies for treatment of pathological diseases. The dual receptor antibodies may comprise an antibody to ActRII receptors and may be used to treat pathological condition. The pathological conditions can comprise muscle wasting diseases or any disease that requires stimulation of muscle growth.

First claim

1 . An isolated antigen-binding protein comprising a first polypeptide having at least 97% identity to SEQ ID NO: 15 and a second polypeptide having at least 97% sequence identity to SEQ ID NO: 16.

2 . An isolated antigen-binding protein comprising SEQ ID NO: 15 and SEQ ID NO: 16.

3 . The isolated antigen-binding protein of claim 1 or 2 that specifically binds to SEQ ID NO: 2 and SEQ ID NO: 18.

4 . The antigen-binding protein of claim 1 or 2 , that specifically binds to SEQ ID NO: 2 and SEQ ID NO: 18 and upon binding, stimulates muscle growth.

5 . The antigen-binding protein of claim 1 or 2 , wherein said antigen-binding protein is a monoclonal antibody or fragment thereof.

6 . The antigen-binding protein of claim 1 or 2 , wherein said antigen-binding protein is a mouse antibody, a humanized antibody, a human antibody, a chimeric antibody, a multispecific antibody, or fragment of a mouse antibody, a humanized antibody, a chimeric antibody or a multispecific antibody.

7 . An isolated antigen-binding protein that binds two activin receptors.

8 . The isolated antigen-binding protein of claim 7 that specifically binds to SEQ ID NO. 2 and SEQ ID NO: 18.

9 . The antigen-binding protein of claim 7 , that specifically binds to SEQ ID NO: 2 and SEQ ID NO: 18 and, upon binding, stimulates muscle growth.

10 . The antigen-binding protein of claim 7 , wherein said antigen-binding protein is a monoclonal antibody or fragment thereof.

11 . The antigen-binding protein of claim 7 , wherein said antigen-binding protein is a mouse antibody, a humunized antibody, a human antibody, a chimeric antibody, a multispecific antibody, or fragment of a mouse antibody, a humunized antibody, a chimeric antibody or a multispecific antibody.

12 . An isolated antigen-binding protein comprising SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.

13 . The isolated antigen-binding protein of claim 12 that specifically binds to SEQ ID NO: 2 and SEQ ID NO: 18.

14 . The antigen-binding protein of claim 12 , that specifically binds to SEQ ID NO: 2 and SEQ ID NO: 18 and upon binding, stimulates muscle growth.

15 . The antigen-binding protein of claim 12 , wherein said antigen-binding protein is a monoclonal antibody or fragment thereof.

16 . The antigen-binding protein of claim 12 , wherein said antigen-binding protein is a mouse antibody, a humunized antibody, a human antibody, a chimeric antibody, a multispecific antibody, or fragment of a mouse antibody, a humunized antibody, a chimeric antibody or a multispecific antibody.

17 . An isolated antigen-binding protein comprising SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5.

18 . The isolated antigen-binding protein of claim 17 that specifically binds to SEQ ID NO: 2 and SEQ ID NO: 18.

19 . The antigen-binding protein of claim 17 , that specifically binds to SEQ ID NO: 2 and SEQ ID NO: 18 and upon binding, stimulates muscle growth.

20 . The antigen-binding protein of claim 17 , wherein said antigen-binding protein is a monoclonal antibody or fragment thereof.

21 . The antigen-binding protein of claim 17 , wherein said antigen-binding protein is a mouse antibody, a humunized antibody, a human antibody, a chimeric antibody, a multispecific antibody, or fragment of a mouse antibody, a humunized antibody, a chimeric antibody or a multispecific antibody.

22 . An isolated antigen-binding protein comprising SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.

23 . The isolated antigen-binding protein of claim 22 , that specifically binds to SEQ ID NO: 2 and SEQ ID NO: 18.

24 . The antigen-binding protein of claim 22 , that specifically binds to SEQ ID NO: 2 and SEQ ID NO: 18 and upon binding, stimulates muscle growth.

25 . The antigen-binding protein of claim 22 , wherein said antigen-binding protein is a monoclonal antibody or fragment thereof.

26 . The antigen-binding protein of claim 22 , wherein said antigen-binding protein is a mouse antibody, a humanized antibody, a human antibody, a chimeric antibody, a multispecific antibody, or fragment of a mouse antibody, a humanized antibody, a chimeric antibody or a multispecific antibody.

27 . An isolated nucleic acid encoding the antigen-binding protein of claim 22 .

28 . An expression vector comprising the nucleic acid of claim 27 .

29 . A host cell comprising the vector of claim 28 .

30 . The host cell of claim 29 wherein the cell is a eukaryotic or prokaryotic cell.

31 . The host cell of claim 30 wherein the eukaryotic cell is a mammalian cell.

32 . An isolated antigen-binding protein, comprising at least SEQ ID NOs: 3-5 or SEQ ID NOs: 4-6.

33 . A method of producing an antigen-binding protein, comprising culturing the host cell of claim 29 under suitable conditions such that the nucleic acid is expressed to produce the antibody.

34 . The method of claim 33 , further comprising recovering the antibody from a culture of the host cell.

35 . A composition comprising the antigen-binding protein of claim 1 and a pharmaceutically acceptable carrier, diluent or excipient.

36 . A method of reducing or blocking myostatin, activin A or GDF-11 activity comprising administering a therapeutically effective amount of the antigen-binding protein or a pharmaceutical composition containing the antigen binding protein of claim 1 to a in need of such treatment.

37 . A method of increasing lean muscle mass or increasing the ratio of lean muscle mass to fat mass in a subject in need of such treatment comprising administering an effective amount the antigen-binding protein or a pharmaceutical composition containing the antigen binding protein of claim 22 to a subject in need of such treatment.

38 . A method of treating or preventing a muscle wasting disease in a subject suffering from such a disorder comprising administering an effective amount of a therapeutic composition containing the antigen-binding polypeptide of claim 1 to the subject.

39 . The method of claim 38 wherein the muscle wasting disease comprises cancer cachexia, muscular dystrophy, amyotrophic lateral sclerosis, congestive obstructive pulmonary disease, chronic hear failure, chemical cachexia, cachexia from HIV/AIDS, renal failure, uremia, rheumatoid arthritis, age-related sarcopenia, age-related frailty, organ atrophy, carpal tunnel syndrome, androgen deprivation, or muscle-wasting due to inactivity from prolonged bed rest, spinal cord injury, stroke, bone fracture, burns, aging or insulin resistance.

40 . An isolated antigen-binding protein of claim 1 wherein said antigen-binding protein has a K D for ActRIIB of 10 pM or less in BIAcore assay.

41 . The antigen-binding protein of claim 40 wherein said antigen-binding protein has a K D for ActRIIB of 1 pM or less.

42 . An isolated antigen-binding protein of claim 1 wherein said antigen-binding protein has a K D for ActRIIA of 4 nM or less in BIAcore assay.

43 . The antigen-binding protein of claim 42 wherein said antigen-binding protein also has a K D for ActRIIA of 1 pM or less.

44 . An anti

Assignees

• Amgen Inc

Inventors

• Han Huiquan
• Zhou Xiaolan
• Chen Qing
• Tsai Mei-Mei

Classifications

• C07K2317/75

  Agonist effect on antigen · CPC title

• C07K16/42

  against immunoglobulins · CPC title

• C07K2317/31

  multispecific · CPC title

• C07K16/468

  Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies · CPC title

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title